Accumulating evidence over the last decade indicates that cytomegalovirus (CMV) is a major cause of the immunological changes that accompany aging, and that it contributes to multiple inflammatory processes and mortality in the elderly. This project will analyze data from the third National Health and Examination Survey (NHANES III, 1998-2002) to determine whether people infected with cytomegalovirus (CMV) are at greater risk for several chronic inflammatory conditions commonly associated with aging (cardiovascular disease, cognitive decline, frailty and osteoporosis), as well as for increased mortality, both all-cause and attributable to cardiovascular disease or cancer. These endpoints were chosen based on literature reports that CMV- associated biomarkers predict the incidence of the disease or premature mortality. However, because CMV seropositivity is so high in the elderly, and most studies were small, all but two of the previous studies have been limited to reporting associations with biomarkers of a large immune response to CMV, rather than comparing the risk in CMV seropositives versus seronegatives. Since there are alternative explanations for an association between the size of the immune response to CMV and poor aging, it is important to analyze data from a study large enough to obtain a valid statistical comparison between CMV-seropositive and CMV- seronegative individuals. NHANES III reports CMV serology on 5,298 participants over the age of 60, of whom 86% were seropositive. Preliminary analysis indicated that the datasets for the disease and mortality outcomes above contain sufficient cases for valid statistical analysis. We will perform Cox proportional hazard regression modeling to determine the relative risk attributable to CMV, after adjusting for all possible confounders that are overrepresented in the CMV seropositive group. Additional, more exploratory analyses will be performed to guide design of future studies. These include analysis of interactions between inflammatory markers, CMV and outcome, and to determine the age and gender groups most at risk for CMV-exacerbated disease. PUBLIC HEALTH RELEVANCE: As the population ages, there is increasing effort to increase the "health-span" - i.e. the period of life in which individuals experience good health and quality of life. Inflammation is thought to be the underlying cause of many conditions that most impact health in this age group, including cardiovascular disease, cognitive decline and frailty. CMV is an infectious disease that has been implicated in these conditions, and that may contribute to inflammation. However, there is valid concern that some of the associations with CMV may have been misinterpreted. It is important to be certain whether CMV is causally involved in these conditions. If CMV is causally involved (a) anti-viral drugs might be useful adjuncts to treatment or prevention, especially if safer anti-virals can be developed, and (b) reducing the rate of CMV infection, either by vaccine development or by reducing exposure, would be a powerful public health measure.